Dissection of the Molecular Events Occurring During T Cell Cycle Progression
For the first time it has been possible to study the events occurring subsequent to T cell receptor activation with reasonable certainty that the experimental results can be interpreted correctly. We stand at this threshold as a consequence of the identification of the Ti-Tn complex as the receptor for antigen, and the generation of both antagonistic and agonistic monoclonal antibodies reactive with this receptor (1–9). Thus, it has been discerned that activation of T-T3 leads to a rapid (within minutes) increase in intracellular free calcium, and translocation of the calcium-dependent protein kinase (c-kinase) from the cytosol to the membrane (12,13). Subsequently, within a few hours, it is possible to detect transcription of several genes, including those encoding interleukin 2 (IL-2), IL-2 receptors, interferon gamma (IFN-γ) and the c-myc proto-onncogene (14). Moreover, the genes encoding the IL-2 receptor, IFN-γ and c-myc are induced coordinately even in the presence of cycloheximide, thereby suggesting that a simple pre-existing biochemical pathway is responsible for activating these genes (14). However, despite the recognition that activation of both the antigen receptor and the IL-2 receptor are required for T cell proliferation, the precise function of each of these receptors as regards movement of the t cell through the cell cycle has remained obscure. Thus, it has been unclear as to whether activation of the T cell antigen receptor complex promotes movement of the cells through G1 to a point that requires IL-2 just before S-phase, or whether IL-2 itself is responsible for G1 progression.
KeywordsChicken Embryo Fibroblast Intracellular Free Calcium Cell Antigen Receptor Cell Receptor Activation Cytoplasmic Free Calcium
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